Recent Advances in Our Understanding of the Link between the Intestinal Microbiota and Systemic Lupus Erythematosus

• Published in: International journal of molecular sciences Vol. 20; no. 19; p. 4871
• Main Authors: Kim, Ji-Won, Kwok, Seung-Ki, Choe, Jung-Yoon, Park, Sung-Hwan
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 30.09.2019; MDPI
• Subjects: Animal models; Animals; Antibodies, Antinuclear; Antibody response; Antigens; Apoptosis; Arthritis; Autoantibodies; Autoimmune diseases; Autoimmunity; Bacteria; Chronic conditions; Commensals; Cytokines; Deoxyribonucleic acid; Digestive system; Disease; Disease Models, Animal; Disease Susceptibility; DNA; Epitopes; Gastrointestinal Microbiome - immunology; Genomes; Homeostasis; host microbial interactions; Humans; Immune system; Inflammation; Interferon; interferon type i; Intestinal microflora; Lupus; Lupus Erythematosus, Systemic - etiology; Lupus nephritis; Lymphocytes; Metabolism; Microbiomes; Microbiota; Microorganisms; Mimicry; molecular mimicry; Molecular Mimicry - immunology; Nephritis; Next-generation sequencing; Obesity; Organs; Pathogenesis; Review; Small intestine; Systemic lupus erythematosus; microbiota; molecular mimicry; systemic lupus erythematosus; host microbial interactions; autoantibodies; interferon type I
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms20194871

Systemic lupus erythematosus (SLE) is an autoimmune disease featuring enhanced expression of type I interferon (IFN) and autoantibody production triggering inflammation of, and damage to, multiple organs. Continuing research efforts focus on how gut microbes trigger systemic autoimmunity and SLE. The gut microbial communities of mice and humans with lupus have been investigated via high-throughput sequencing. The Firmicutes-to-Bacteroidetes ratio is consistently reduced in SLE patients, regardless of ethnicity. The relative abundance of differs from the animal model used (MRL/lpr mice or NZB/W F1 mice). This may indicate that interactions between gut microbes and the host, rather than the enrichment of certain gut microbes, are especially significant in terms of SLE development. and , both of which are possible gut pathobionts, become translocated into systemic tissue if the gut epithelial barrier is impaired. The microbes then interact with the host immune systems, activating the type I IFN pathway and inducing autoantibody production. In addition, molecular mimicry may critically link the gut microbiome to SLE. Gut commensals of SLE patients share protein epitopes with the Ro60 autoantigen. strain cross-reacted with native DNA, triggering an anti-double-stranded DNA antibody response. Expansion of in SLE patients paralleled an increase in disease activity and lupus nephritis. Such insights into the link between the gut microbiota and SLE enhance our understanding of SLE pathogenesis and will identify biomarkers predicting active disease.